The UCSF Alzheimer's Disease Research Center (ADRC) has made remarkable progress in our first 9 years, developing diagnostic approaches to dementia that are elucidating the phenotypic, genetic and molecular heterogeneity of Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). The unique clinical cohorts, biospecimens, and images that we collect in the ADRC have facilitated these successes. Talented scientists mentored through our ADRC are making major contributions to the understanding of dementia. ADRC research has steadily increased. We are defining distinctive clinical subtypes of AD, FTD, and CJD that predict specific molecular and physiological mechanisms for dementia, while improving early recognition and tracking of transitions from normal aging to mild cognitive impairment (MCI) and dementia. These efforts will continue in parallel with drug development and pursuit of clinical trials with researchers who work with the ADRC. We will explore the heterogeneous features of AD, FTD-spectrum disorders, and CJD in the early stages with the goal of predicting their physiological, genetic, and molecular underpinnings. We will leverage cohorts in the ADRC and the powerful neuroscience community at UCSF and beyond to stimulate new diagnostic and treatment efforts for AD, FTD and CJD. We will increase understanding of the unique cultural and biological features of aging Chinese-Americans. We will develop innovative approaches to data management and biostatistics that we will share. The Education Core will be responsible for training new dementia leaders, while educating the medical and lay communities about non-AD dementias and non-amnestic subtypes of AD. We will perform three new projects: Project 1: Dr. Gil Rabinovici will compare and contrast early onset AD, late onset AD, and apoE4+ versus apoE4- patients to improve diagnostic accuracy in AD. Project 2: Dr. Marilu Gorno-Tempini will study developmental and immunological factors that influence the phenotype in PPA. Project 3: Dr. Yadong Huang will reprogram human skin fibroblasts into induced pluripotent stem cells and convert them into neurons from E4/E4 or E3/3 patients and healthy controls. Pathological substrates and gene expression will be compared.